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Ketoconazole (Topical)

Class: Azoles
VA Class: DE102
Chemical Name: cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl] methoxy]phenyl] piperazine
Molecular Formula: C26H28Cl2N4O4
CAS Number: 65277-42-1
Brands: Extina, Nizoral, Nizoral A-D, Xolegel

Medically reviewed by Drugs.com. Last updated on June 22, 2020.

Introduction

Antifungal; azole (imidazole derivative).

Uses for Ketoconazole (Topical)

Dermatophytoses

Treatment of tinea corporis, tinea cruris, and tinea pedis caused by Epidermophyton floccosum, Trichophyton mentagrophytes, or T. rubrum.

A drug of first choice for topical treatment of tinea corporis or tinea cruris. Oral antifungals preferred when tinea corporis or tinea cruris is extensive, dermatophyte folliculitis is present, infection is chronic or does not respond to topical therapy, or patient is immunocompromised or has coexisting disease.

Treatment of tinea manuum caused by Trichophyton and tinea corporis caused by Microsporum.

Cutaneous Candidiasis

Treatment of cutaneous candidiasis caused by Candida albicans.

Pityriasis (Tinea) Versicolor

Treatment of pityriasis (tinea) versicolor caused by or presumed to be caused by Malassezia furfur (Pityrosporum orbiculare or P. ovale).

Seborrheic Dermatitis and Dandruff

Treatment of seborrheic dermatitis, including seborrheic dermatitis of the scalp.

Self-medication (OTC use) for reduction of flaking, scaling, and itching associated with dandruff.

Ketoconazole (Topical) Dosage and Administration

Administration

Topical Administration

Apply topically to skin as a 2% cream, foam, gel, or shampoo.

Apply topically to hair and scalp as a 1% shampoo. Also has been applied topically to hair and scalp as a 2% shampoo.

Cream, foam, gel, and shampoo are for external use only. Do not apply to eyes and do not administer orally or intravaginally.

If contact with eyes, mouth, or vagina occurs, rinse thoroughly with water.

When using the 2% foam, hold the can containing the foam upright and spray a small amount into the cap of the can or other cool surface. Do not dispense foam directly onto affected areas or onto hands since the foam will begin to melt immediately on contact with warm skin. If fingers are warm, rinse them in cold water and dry before handling the foam. Using the fingertips, gently massage small amounts of foam onto affected areas until the foam disappears and entire affected area has been treated.

When using the 2% gel, do not apply sunscreen or cosmetics to the affected area until at least 20 minutes after application of the gel. Do not wash the affected area for at least 3 hours after application of the gel.

Avoid fire, flame, and/or smoking during and immediately after application of 2% foam or gel. (See Flammability under Cautions.)

Dosage

Pediatric Patients

Topical Seborrheic Dermatitis in Children ≥12 Years of Age

2% gel: Apply to affected areas once daily for 2 weeks.

2% foam: Apply to affected areas twice daily for 4 weeks.

Dandruff in Children ≥12 Years of Age
Topical

1% shampoo: For self-medication, apply to wet hair, lather, and rinse thoroughly; then repeat application, lathering, and rinsing. Use every 3 or 4 days for up to 8 weeks as needed or as directed by a clinician. Thereafter, use as needed to control dandruff.

Adults

Dermatophytoses
Tinea Corporis or Tinea Cruris
Topical

2% cream: Apply and rub gently into affected and surrounding area of skin once or twice daily for 2 weeks. There is some evidence that twice-daily regimen may occasionally be more effective than once-daily regimen. If clinical improvement does not occur after treatment, reevaluate diagnosis.

Tinea Pedis
Topical

2% cream: Apply and rub gently into affected and surrounding area of skin once or twice daily for 6 weeks. If clinical improvement does not occur after treatment, reevaluate diagnosis.

Moccasin-type (dry-type) tinea pedis may require more prolonged therapy.

Cutaneous Candidiasis
Topical

2% cream: Apply and rub gently into affected and surrounding area of skin once or twice daily for 2 weeks. If clinical improvement does not occur after treatment, reevaluate diagnosis.

Pityriasis (Tinea) Versicolor
Topical

2% cream: Apply and rub gently into affected and surrounding area of skin once daily for 2 weeks. If clinical improvement does not occur after treatment, reevaluate diagnosis.

2% shampoo: Apply to damp skin of the affected area and a wide margin surrounding this area and lather; after 5 minutes, rinse with water. A single application should be sufficient, although once-daily application for 3 days also has been used.

Seborrheic Dermatitis
Topical

2% cream: Apply and rub gently into affected areas twice daily for 4 weeks or until clinical clearing.

2% foam: Apply and gently massage into affected areas twice daily for 4 weeks.

2% gel: Apply to affected areas once daily for 2 weeks.

2% shampoo: For seborrheic dermatitis of the scalp, has been used to wash the hair and scalp 2 or 3 times weekly for 2–4 weeks. After a response was obtained, has been used once weekly every other week to prevent relapse.

Dandruff
Topical

1% shampoo: For self-medication to control flaking, scaling, and itching associated with dandruff, apply to thoroughly wet hair, lather and rinse thoroughly; then repeat application, lathering, and rinsing. Use every 3 or 4 days for up to 8 weeks as needed or as directed by a clinician. Thereafter, use as needed to control dandruff.

2% shampoo: For treatment of dandruff, has been used to wash the hair and scalp 2 or 3 times weekly for 2–4 weeks. After a response was obtained, has been used once weekly every other week to prevent relapse.

Cautions for Ketoconazole (Topical)

Contraindications

  • Hypersensitivity to ketoconazole or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Contact dermatitis reported following topical application of ketoconazole or other imidazole-derivative azole antifungals.

If a reaction suggesting sensitivity or chemical irritation occurs (e.g., rash), discontinue the drug.

Possible cross-sensitization among the imidazole derivatives.

Sulfite Sensitivity

Some formulations of the 2% cream contain sodium sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals. Overall prevalence of sulfite sensitivity in the general population is unknown, but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.

General Precautions

Systemic Adverse Effects

Although hepatotoxicity, decreased testosterone concentrations, and decreased ACTH-induced corticosteroid concentrations have been reported with oral ketoconazole, these adverse effects have not been reported with topical ketoconazole and are unlikely since the drug does not appear to be appreciably absorbed following topical application to skin.

Flammability

2% foam and gel are flammable. Avoid fire, flame, and/or smoking during and immediately after application of foam or gel. (See Storage under Stability.)

Specific Populations

Pregnancy

Category C.

2% cream, foam, gel, or shampoo: Use during pregnancy only when potential benefits justify possible risks to the fetus.

1% shampoo: Pregnant women considering self-medication should consult a clinician before using the preparation.

Lactation

Not known whether ketoconazole distributed into milk following topical application.

2% cream: Discontinue nursing or the cream.

2% foam, gel, or shampoo: Use with caution.

1% shampoo: Nursing women considering self-medication should consult clinician before using the preparation.

Pediatric Use

2% cream: Safety and efficacy not established in children; has been used without unusual adverse effect in children 2 days to 12 years of age.

2% foam: Safety and efficacy not established in children <12 years of age.

2% gel: Safety and efficacy not established in children <12 years of age.

1% shampoo: Safety and efficacy for self-medication not established in children <12 years of age.

2% shampoo: Safety and efficacy not established in children.

Common Adverse Effects

2% cream: Local reactions at application site (severe irritation, pruritus, stinging).

2% foam: Application site reactions (e.g., burning).

2% gel: Application site reactions (e.g., burning), headache.

2% shampoo: When applied to the skin, pruritus, application site reaction, dry skin. When applied to scalp, increased hair loss, irritation, abnormal hair texture, loss of hair curl in patients with permanently waved (“permed”) hair, scalp pustules, dry skin, pruritus, oiliness or dryness of the hair and scalp.

Interactions for Ketoconazole (Topical)

No formal drug interaction studies to date.

Ketoconazole (Topical) Pharmacokinetics

Absorption

Bioavailability

Ketoconazole does not appear to be appreciably absorbed systemically following topical application to skin or scalp.

2% cream: Topical application to chest, back, and arms of healthy adults with intact skin does not result in detectable blood concentrations. Following topical application in vitro in a skin model, ketoconazole was retained in the stratum corneum and the boundary of the stratum corneum and stratum granulosum for up to 16 hours.

2% foam: Topical application of 3 g twice daily for 4 weeks in patients with moderate to severe seborrheic dermatitis resulted in plasma ketoconazole concentrations <6 ng/mL in 75% of patients; maximum plasma concentration was 11 ng/mL.

2% gel: Topical application once daily for 2 weeks (0.05-3.47 g daily) in patients with severe seborrheic dermatitis (1–14% of body surface area) resulted in mean peak plasma concentrations of 1.35 ng/mL on day 7 and 0.8 ng/mL on day 14.

2% shampoo: Chronic use of 2% shampoo (4–10 times weekly for 6 months, 2–3 times weekly for 3–26 months) did not result in detectable plasma concentrations.

Small amounts of ketoconazole are absorbed systemically when the drug is administered intravaginally.

Distribution

Extent

Not known whether ketoconazole distributed into milk following topical application of 2% cream, foam, gel, or shampoo.

Stability

Storage

Topical

2% Cream

20–25°C or 15–30°C, depending on manufacturer.

2% Foam

20–25°C; do not refrigerate or freeze.

Flammable; do not store in direct sunlight and do not expose to heat or temperatures >49°C. Do not puncture and/or incinerate container.

2% Gel

25°C (may be exposed to 15–30°C).

1% Shampoo

2–30°C; protect from light and freezing.

2% Shampoo

≤25°C; protect from light.

Actions and Spectrum

  • Imidazole-derivative azole antifungal.

  • Structurally related to other imidazole-derivative azole antifungals (e.g., butoconazole, clotrimazole, econazole, miconazole, oxiconazole, sulconazole, tioconazole).

  • Usually fungistatic; may be fungicidal at high concentrations after prolonged incubation or against very susceptible organisms.

  • Presumably exerts its antifungal activity by altering cellular membranes, resulting in increased membrane permeability, secondary metabolic effects, and growth inhibition. Fungistatic activity may result from interference with ergosterol synthesis. Fungicidal activity at high concentrations may result from a direct physiochemical effect on the fungal cell membrane.

  • Mechanism(s) of action in the treatment of dandruff not fully determined.

  • Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes.

  • Dermatophytes: Active against Epidermophyton floccosum, Microsporum audouini, M. canis, M. gypseum, Trichophyton mentagrophytes, T. rubrum, and T. tonsurans.

  • Other fungi: Active against Candida albicans, C. tropicalis, and Malassezia furfur (Pityrosporum orbiculare, P. ovale).

Advice to Patients

  • Importance of using the medication for the full, prescribed treatment period, even if symptoms improve; importance of consulting with clinician if the skin condition does not improve after a full course of therapy.

  • Importance of discontinuing use and contacting clinician if signs or symptoms of irritation or sensitization occur.

  • Importance of not applying 2% cream, foam, or gel to eyes or intravaginally.

  • If using 2% foam or gel, importance of avoiding fire, flame, and/or smoking during and immediately following application. Importance of not throwing foam container into a fire, even if can is empty.

  • If using shampoo, importance of avoiding contact with eyes; if contact with eyes occurs, rinse thoroughly with water.

  • Importance of not using the 1% shampoo for self-medication of dandruff if the scalp is broken or inflamed. Importance of discontinuing use and contacting a clinician if rash occurs or the condition worsens or does not improve within 2–4 weeks.

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, or any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ketoconazole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

2%*

Ketoconazole Cream

Foam

2%

Extina

Stiefel

Gel

2%

Xolegel

Barrier Therapeutics

Shampoo

1%

Nizoral A-D

McNeil

2%*

Ketoconazole Shampoo,

Nizoral

Ortho-McNeil

AHFS DI Essentials™. © Copyright 2021, Selected Revisions July 1, 2009. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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